chr6-31949763-T-C

Position:

• chr6-31949763-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001710.6(CFB):​c.1408+206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 722,146 control chromosomes in the GnomAD database, including 42,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6791 hom., cov: 32)
  • Exomes 𝑓: 0.34 (35569 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.680

Genes affected

CFB (HGNC:1037): (complement factor B) This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-31949763-T-C is Benign according to our data. Variant chr6-31949763-T-C is described in ClinVar as [Benign]. Clinvar id is 1259216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFB	NM_001710.6	c.1408+206T>C		intron_variant		ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7	c.1408+206T>C		intron_variant		1	NM_001710.6	ENSP00000416561	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41185 AN: 150326 Hom.: 6792 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.344 AC: 196586 AN: 571696 Hom.: 35569 Cov.: 7 AF XY: 0.346 AC XY: 104317 AN XY: 301402

Gnomad4 AFR exome AF: 0.0774

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.527

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.274 AC: 41184 AN: 150450 Hom.: 6791 Cov.: 32 AF XY: 0.277 AC XY: 20333 AN XY: 73530

Gnomad4 AFR AF: 0.0814

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.288

Alfa AF: 0.355 Hom.: 19301

Bravo AF: 0.261

Asia WGS AF: 0.256 AC: 894 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4151657; hg19: chr6-31917540;